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PubMed1996

A model conforming the decline in follicle numbers to the age of menopause in women.

The store of primordial follicles in the ovary is fixed before birth and dwindles with age until it is unable to provide enough Graafian stages to sustain menstrual cyclicity. According to a simple bi-exponential model of ageing, the rate of follicle disappearance increases at age 37.5 years (or when 25 000 follicles remain) so that the numbers fall to approximately 1000 at 51 years, the median age of menopause in the population. This study attempts to produce a biologically more realistic model of follicle disappearance and harmonizes follicle dynamics with the distribution of menopausal ages from an American survey. The step-change in the rate of follicle attrition was replaced by a model which assumed that this rate changes more gradually with the size of the follicle store. This produced a distribution of predicted menopausal ages (based on an assumed threshold of 1000 follicles) which was closer to observed data. The fit further improved when the model was modified by having a threshold that varied across the population. Using such a stochastic threshold model for menopause, the number of fertile years remaining could be forecast with an acceptable margin of uncertainty if it ever becomes possible to estimate the size of the follicle store in vivo.

Adult↗
PubMed2006

A photoelectron and TPEPICO investigation of the acetone radical cation.

The valence shell photoelectron spectrum, threshold photoelectron spectrum, and threshold photoelectron photoion coincidence (TPEPICO) mass spectra of acetone have been measured using synchrotron radiation. New vibrational progressions have been observed and assigned in the X 2B2 state photoelectron bands of acetone-h6 and acetone-d6, and the influence of resonant autoionization on the threshold electron yield has been investigated. The dissociation thresholds for fragment ions up to 31 eV have been measured and compared to previous values. In addition, kinetic modeling of the threshold region for CH3* and CH4 loss leads to new values of 78 +/- 2 kJ mol(-1) and 75 +/- 2 kJ mol(-1), respectively, for the 0 K activation energies for these two processes. The result for the methyl loss channel is in reasonable agreement with, but slightly lower than, that of 83 +/- 1 kJ mol(-1) derived in a recent TPEPICO study by Fogleman et al. The modeling accounts for both low-energy dissociation channels at two different ion residence times in the mass spectrometer. Moreover, the effects of the ro-vibrational population distribution, the electron transmission efficiency, and the monochromator band-pass are included. The present activation energies yield a Delta(f)H298 for CH3CO+ of 655 +/- 3 kJ mol(-1), which is 4 kJ mol(-1) lower than that reported by Fogleman et al. The present Delta(f)H298 for CH3CO+ can be combined with the Delta(f)H298 for CH2CO (-47.5 +/- 1.6 kJ mol(-1)) and H+ (1530 kJ mol(-1)) to yield a 298 K proton affinity for ketene of 828 +/- 4 kJ mol(-1), in good agreement with the value (825 kJ mol(-1)) calculated at the G2 level of theory. The measured activation energy for CH4 loss leads to a Delta(f)H298 (CH2CO+*) of 873 +/- 3 kJ mol(-1).

Journal Article↗
PubMed1997

The effects of focal N-methyl-D-aspartate pretreatment on the parameters of amygdaloid electrical kindling.

Evidence is accumulating for a role of glutamate in both the development (epileptogenesis) and spread of epileptic neuronal hyperactivity in the brain. In the present investigation we examined the influence of daily focal pretreatment with the selective glutamate receptor agonist N-methyl-D-aspartate (NMDA) on the parameters of amygdaloid electrical kindling, an animal model of human complex partial and secondary generalised focal seizures. Pretreatment with NMDA significantly increased the electrical afterdischarge threshold in this model. With subsequent daily suprathreshold electrical stimulation, however, NMDA pretreatment enhanced the kindling process as shown by both electroencephalographic and motor seizure responses. Marked reductions in the number of stimulations required to reach each distinct stage of kindling development were evident. The number of stimulations required to achieve the fully kindled state was approximately halved by pretreatment with NMDA (6.8 +/- 1.6 stimulations) compared with control, buffer-pretreated animals (11.6 +/- 1.4 stimulations; mean +/- S.E.M.; P < 0.05). Consistent with this, the mean durations of the electrically-evoked afterdischarges on most NMDA pretreatment days were significantly increased compared to those recorded in control animals. Importantly, fully kindled animals showed a markedly enhanced sensitivity to focally applied NMDA. The results of the present experiments provide strong in vivo evidence to support the concept that ion fluxes through NMDA receptor-linked cation channels play a major role in the mechanisms of kindling epileptogenesis. Extracellular glutamate at abnormally raised levels, acting at least in part via NMDA receptors, may be the principal agent triggering many forms of epilepsy.

Amygdala↗
PubMed1984

Spatial selectivity of contrast adaptation: models and data.

Contrast threshold elevation was measured in human observers at a single spatial frequency (4 or 8 c/deg) after adaptation to gratings at different contrasts and spatial frequencies. When plotted against adapting contrast, the threshold elevation functions for different adapting frequencies were neither straight nor parallel, which poses difficulties for the "equivalent contrast transformation". The different functions appear to form a single family, differing by a scaling factor that depends on spatial frequency but is independent of contrast. This is similar to expressing the aftereffect as a proportion of its peak value. A multiple channel, "fatigue" model of adaptation is shown to be consistent with the results, provided the channel shape is appropriate and channels overlap considerably in the frequency domain. Channel bandwidth is estimated at 1.4 octaves, similar to that of cortical cells.

Adaptation, Ocular↗
PubMed1992

Time-dependent thresholds for torpor initiation in the rufous hummingbird (Selasphorus rufus).

Three models for torpor initiation were tested in rufous hummingbirds (Selasphorus rufus) during moult, when these birds appear to avoid the use of torpor. In model 1, the level of energy reserves at which torpor is initiated (the "threshold") remains constant throughout the night. In model 2, the threshold declines throughout the night, at a constant rate equivalent to the rate at which energy reserves are depleted during torpor. In model 3, the threshold declines at a rate equivalent to the rate of energy reserve depletion during torpor for most of the night, but at a higher rate (corresponding to the rate of energy expenditure during normothermia) during the final 2 h of the night, when these birds are usually normothermic. Model 1 predicts the most frequent and longest bouts of torpor, whereas model 3 predicts the fewest and shortest bouts. To determine the thresholds for each of 12 birds, food supply was manipulated to induce entry into torpor at different times on successive nights. Threshold slopes matched the predictions of model 3 most closely. Calculations comparing observed incidence of torpor with the predictions of model 1 show that the actual, time-dependent threshold for torpor initiation resulted in a 72% reduction in the number of torpor bouts compared with the number of torpor bouts that should have been initiated by a constant threshold. The advantage of a time-dependent threshold is that, although torpor is initiated when needed to prevent energy reserves from falling below a critical level, the amount of time spent in torpor can be minimized.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Modulation detection and discrimination with three-component signals.

In an attempt to study the processing of amplitude and frequency modulation (AM and FM), detection and discrimination tasks using mixed modulation (MM) signals were performed. Modulation detection thresholds were obtained for three-component signals that span the parameter space between AM and quasi-FM. A single-cue modulation detection model predicts the thresholds with reasonable accuracy. If one assumes that the AM and FM components are extracted separately, thresholds are also well predicted if the d' of the MM signals is equal to the sum of the separate d's of the AM and FM components (two-cue summation model). This could arise from common internal noise that puts the AM and FM information along a single decision axis. A modulation discrimination task was then examined in which the subjects discriminate between signals with both different modulation depths and different modulation types. The single-cue model predicts performance well. In order for the two-cue model to predict the results, the AM and FM cues must be combined into a single statistic before a decision can be made; the listener cannot process the cues separately.

Adult↗
PubMed1997

BW1003C87, phenytoin and carbamazepine elevate seizure threshold in the rat amygdala-kindling model of epilepsy.

We examined the anticonvulsant effects of BW1003C87 (5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine ethane sulphonic acid), which is structurally related to the new antiepileptic drug, lamotrigine, and compared its effects to those of the conventional antiepileptic drugs, phenytoin and carbamazopine, using the rat amygdala-kindling model of epilepsy. BW1003C87 (2.5-10 mg/kg, i.p.) had potent and long-lasting (48 h after single administration) effects on amygdala-kindled seizures. The effects of BW1003C87 were completely reversed when the stimulus intensity was increased to 2 or 3 times the threshold determined. Since the same effects on seizure threshold were obtained for phenytoin and carbamazepine in the present study and for lamotrigine in our previous study, we propose that the principal mechanism of these antiepileptic drugs, which act primarily on voltage-sensitive Na+ channels, is significant elevation of the seizure threshold in epileptogenic foci and that BW1003C87 has a profile similar to that of these drugs.

Amygdala↗
PubMed2005

A functional point-neuron model simulating cochlear nucleus ideal onset responses.

Cochlear nucleus neurons revealing ideal onset (OI)-type peri-stimulus time histograms (PSTH) encode temporal features of acoustic stimuli with very high precision. These neurons are therefore assumed to be involved in the recognition of natural sounds with temporally varying envelopes such as speech. A functional point-neuron model is presented here for the simulation of OI-unit responses found in cochlear nucleus octopus cells. The model assumes a biphasic response of the membrane potential to a current impulse, the membrane impulse response, and a dynamic spike-blocking mechanism. The predicted responses to pure tones at low and high frequencies, injected current steps, and amplitude modulated tones are compared to recordings from the literature. The model accounts for the main response properties in the data using the same small set of parameters for all experimental conditions. The assumed biphasic shape of the membrane impulse response, reflecting a higher sensitivity to stimulus transients and fast changes relative to sustained stimulus portions, allows for a description of OI-unit responses that cannot be accounted for by a coincidence detector model with an integrate-to-threshold dynamic. The presented functional model may be useful as a processing module in more complex models of auditory signal processing and perception.

Acoustic Stimulation↗
PubMed2002

Hearing threshold levels for an otologically unscreened, non-occupationally noise-exposed population in Sweden.

The aim of this study was to investigate the hearing threshold levels (HTL) of an otologically unscreened population in Sweden. The results are compared to other studies of otologically unscreened populations, and a new mathematical model of hearing threshold levels as a function of age is presented. The subjects were males and females aged from 19 to 81 years, selected from the province of Ostergötland in Sweden. The test battery included otoscopy, tympanometry, pure-tone audiometry, and a questionnaire. Subjects exposed to occupational noise were excluded, and in total 603 persons were included in the analysis. The regression analysis resulted in different hyperbolic tangent functions with four parameters: HTL=A+B x tanh(C x age+D).

Acoustic Impedance Tests↗
PubMed1993

Phenomenological model for interpreting the clinical significance of the in vitro optical transfer function.

We describe a methodology to predict the outcome of clinical tests caused by changes made to the optical elements of the human eye. This formalism, called the expected visual outcome model, is based on in vitro measurements of the optical transfer function and takes into account a simple model of human threshold performance. The clinical tests under consideration are high-contrast visual acuity and contrast sensitivity. Using the expected visual outcome, we describe a useful performance index called the predicted visual acuity graph, which can be measured clinically. The theoretical results are compared with visual function measured in patients with pseudophakic (multifocal and monofocal) implants.

Cataract Extraction↗
PubMed2003

Optimization of the microbial synthesis of dihydroxyacetone from glycerol with Gluconobacter oxydans.

An optimized repeated-fed-batch fermentation process for the synthesis of dihydroxyacetone (DHA) from glycerol utilizing Gluconobacter oxydans is presented. Cleaning, sterilization, and inoculation procedures could be reduced significantly compared to the conventional fed-batch process. A stringent requirement was that the product concentration was kept below a critical threshold level at all times in order to avoid irreversible product inhibition of the cells. On the basis of experimentally validated model calculations, a threshold value of about 60 kg x m(-3) DHA was obtained. The innovative bioreactor system consisted of a stirred tank reactor combined with a packed trickle-bed column. In the packed column, active cells could be retained by in situ immobilization on a hydrophilized Ralu-ring carrier material. Within 17 days, the productivity of the process could be increased by 75% to about 2.8 kg x m(-3) h(-1). However, it was observed that the maximum achievable productivity had not been reached yet.

Bioreactors↗
PubMed2000

Indices for nutritional condition and thresholds for winter survival in sika deer in Hokkaido, Japan.

We derived fat indices for sika deer (Cervus nippon yesoensis) in eastern Hokkaido, Japan, and estimated the probability of over-winter survival with a logistic regression model using fat indices. Kidney fat mass (KFM) appears to be an adequate index of wide range of physical conditions before the onset of severe nutritional stress. When KFM values fell below 20 g, femur (FMF) and mandible cavity fat (MCF) indices declined sharply. FMF and MCF were useful indices for detecting malnourished deer. A logistic regression model describes survival thresholds in two bone fat indices for calves (45%) and three fat indices for adult females (FMF = 25%, MCF = 30%, KFM = 20 g). These models are useful for estimating the probability of winter survival in Hokkaido sika deer.

Adipose Tissue↗
PubMed2004

Dynamics of T cell activation threshold tuning.

T lymphocytes are believed to alter their sensitivity to TCR stimulation by means of a tunable cellular activation threshold. We present two modelling examples which show that the concept of a tunable threshold can be made mechanistically plausible. The tunable threshold is treated as an emergent property of the dynamics of the T cell's signalling machinery. In addition, we discuss how the dynamic properties of activation threshold tuning can be determined experimentally with the aid of these two models. We propose a novel 'avidity selection' mechanism for the initial stages of the immune response, based on the properties of the T cell activation threshold tuning mechanism we propose for the commitment to differentiation. Our main finding is that activation threshold tuning allows T cells to respond to relevant ligands with a detection threshold that is (i) uniform across both the T cell repertoire and the secondary lymphoid tissues, while (ii) retaining tolerance to autostimulation. Our analysis indicates that central tolerance enhances the efficiency of peripheral tolerance, casting new light on the role of negative selection in the thymus.

Animals↗
PubMed1988

A model to evaluate alternative methods of defibrillation threshold determination.

The voltage (or, equivalently, energy) at which defibrillation occurs for a specific episode of fibrillation can be represented by specifying or estimating the probability of successful defibrillation for each voltage or energy. This relation of voltage to probability is the probability function. For a series of attempts, the probability function predicts the frequency with which defibrillation will occur at a given voltage. By defining the defibrillation threshold (DFT) as the voltage at which the probability function takes on a specific value, say 50%, a method of defibrillation threshold determination can be evaluated by how accurately and precisely it estimates the "true" defibrillation threshold. By utilizing estimated probability functions from animals and humans, the relative performance of different methods of defibrillation threshold determination can be evaluated. Three methods were evaluated using published animal data and human clinical data: (1) stepping down to the first voltage that fails; (2) stepping up to the first voltage that succeeds; and (3) doing both 1 and 2 and averaging. In all cases, Method 3 has lower total error. Definitions of defibrillation threshold other than the 50% level can also be evaluated in this fashion.

Animals↗
PubMed2003

Effect of resiniferatoxin on the noxious heat threshold temperature in the rat: a novel heat allodynia model sensitive to analgesics.

1. An increasing-temperature hot plate (ITHP) was introduced to measure the noxious heat threshold (45.3+/-0.3 degrees C) of unrestrained rats, which was reproducible upon repeated determinations at intervals of 5 or 30 min or 1 day. 2. Morphine, diclofenac and paracetamol caused an elevation of the noxious heat threshold following i.p. pretreatment, the minimum effective doses being 3, 10 and 200 mg kg(-1), respectively. 3. Unilateral intraplantar injection of the VR1 receptor agonist resiniferatoxin (RTX, 0.048 nmol) induced a profound drop of heat threshold to the innocuous range with a maximal effect (8-10 degrees C drop) 5 min after RTX administration. This heat allodynia was inhibited by pretreatment with morphine, diclofenac and paracetamol, the minimum effective doses being 1, 1 and 100 mg kg(-1) i.p., respectively. 4. The long-term sensory desensitizing effect of RTX was examined by bilateral intraplantar injection (0.048 nmol per paw) which produced, after an initial threshold drop, an elevation (up to 2.9+/-0.5 degrees C) of heat threshold lasting for 5 days. 5. The VR1 receptor antagonist iodo-resiniferatoxin (I-RTX, 0.05 nmol intraplantarly) inhibited by 51% the heat threshold-lowering effect of intraplantar RTX but not alpha,beta-methylene-ATP (0.3 micromol per paw). I-RTX (0.1 or 1 nmol per paw) failed to alter the heat threshold either acutely (5-60 min) or on the long-term (5 days). The heat threshold of VR1 receptor knockout mice was not different from that of wild-type animals (45.6+/-0.5 vs 45.2+/-0.4 degrees C). 6. In conclusion, the RTX-induced drop of heat threshold measured by the ITHP is a novel heat allodynia model exhibiting a high sensitivity to analgesics.

Acetaminophen↗
PubMed2003

Statistical performance analysis of signal variance-based dipole models for MEG/EEG source localization and detection.

A set of dipole fitting algorithms that incorporate different assumptions about the variability of the signal component into their mathematical models is presented and analyzed. Dipole fitting is performed by minimizing the squared error between the selected data model and available data. Dipole models based on moments that have 1) constant amplitude and orientation, 2) variable amplitude and fixed known orientation, 3) variable amplitude and fixed unknown orientation, and 4) variable amplitude and variable orientation are considered. The presence of a dipolar source is determined by comparing the fractional energy explained by the dipole model to a threshold. Source localization is accomplished by searching to find the location that explains the largest fractional signal energy using a dipole model. Expressions for the probability of a false positive decision and probability of correct detection are derived and used to evaluate the effect of variability in the dipole on performance and to address the effects of model mismatch and location errors. Simulated and measured data experiments are presented to illustrate the performance of both detection and localization methods. The results indicate that models which account for variance outperform the constant orientation and magnitude model even when the number of observations is relatively small and the signal of interest contains a very modest variance component.

Action Potentials↗
PubMed2002

Dependence of population response to fertility control on the survival of sterile animals and their role in regulation.

The species for which fertility control is presently used, or for which it is being developed, range from small mammal pests, such as the house mouse (Mus domesticus), to large mammals, such as the African elephant (Loxodonta africana). However, the possibility of a population response other than a reduction in abundance proportional to the fraction of animals rendered infertile has been shown in field trials. For example, when intermediate levels of sterility were imposed on wild populations of European rabbits (Oryctolagus cuniculus), there was an increase in their abundance, on an annual basis, due to enhanced survival of juveniles and adult females. In this article, we relate intraspecific regulatory processes to the response of populations to fertility control using a set of density-dependent structured-population models. In each of the models, the population is exposed periodically to a fertility control agent that renders a fraction of fertile females sterile. Although our intention is not to predict the population response of any one particular species, the results of the models are illustrated using parameter values that are representative of populations of the European fox (Vulpes vulpes) in south-eastern Australia. When populations were regulated by density-dependent mechanisms in which sterile females did not participate, such as competition for resources among young animals or competition among fertile females for breeding sites or territories, then populations could increase in abundance for low and intermediate levels of imposed sterility. For other intraspecific regulatory mechanisms, such as competition for resources between all individuals, all levels of sterility were observed to reduce abundance. The population response was sensitive to (i) whether the survival of sterile adults was higher than that of fertile adults, (ii) whether animals could be sterilized before sexual maturity, and (iii) whether density dependence was modelled as a threshold process.

Animals↗